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J Briegel

Publications and source records attributed to J Briegel.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Allogenic liver transplantation: a form of "gene therapy" in metabolic diseases. Munich results and a review].

INTRODUCTION: Liver transplantation is the method of choice for metabolic diseases and end-stage liver failure. METHODS: At the Klinikum Grosshadern we have performed liver transplantation for inborn errors of metabolism in 24 patients (5.3% of all transplantations, 16 adults, age 39 +/- 13 years; 8 children, age 9 +/- 3 years); 19 patients received a transplant for end-stage liver disease, and in 5 cases because of fulminant hepatic failure. RESULTS: Twenty-four patients received 27 transplants. In 3 cases, a split-liver transplantation was performed; one patient received a combined lung-liver graft. The 5-year survival rate for children is 100% and for adults 68%. CONCLUSIONS: Liver transplantation for inborn errors of metabolism not only replaces the diseased organ, but also leads to complete reversal of the metabolic defect.

Adult↗
PubMed2000

Pulmonary function and health-related quality of life in a sample of long-term survivors of the acute respiratory distress syndrome.

OBJECTIVE: We performed a follow-up cohort analysis in order to delineate the correlation between pulmonary function (PF) and health-related quality of life (HRQL) in patients after ARDS. DESIGN: Follow-up cohort study. SETTING: A 20-bed ICU of a university teaching hospital. PATIENTS: A cohort of 50 long-term survivors of ARDS. MEASUREMENTS AND RESULTS: Measurements of PF (FVC, FEV1, TLC, D(LCO)) and HRQL (SF-36 Health Status Questionnaire) were made 5.5 years (median value) after discharge from the ICU. Impairments in PF (defined as PF results below 80% of the predicted value) were frequent but generally mild. Twenty patients had a single PF impairment (with limitations in FEV1/FVC ratio in 12 patients being the most common), four patients had two (with D(LCO) and FEV1/FVC ratio impairment the most common) and three patients had pathologic results in three PF tests (FEV1/FVC ratio, TLC and capillary pO2 during exercise in one case, FVC, TLC and capillary pO2 during exercise in the second patient and FVC, TLC and D(LCO) in the third). Compared to normal controls, survivors of ARDS showed impairments in all SF-36 health dimensions (p < 0.001). Patients with multiple (> 1) PF impairments described the lowest HRQL with major limitations in all SF-36 categories (p < 0.037) including physical and mental summary scores (36.5 vs 46.9, p = 0.037 and 31.3 vs 51.4, p = 0.003) when compared to patients with no or only one PF impairment. CONCLUSIONS: Long-term survivors of ARDS have a significant reduction in HRQL and the presence of multiple PF impairments is associated with maximal decrements in HRQL.

Adult↗
PubMed1999

Response to inhaled nitric oxide (NO) is not associated with changes of plasma cGMP levels in patients with acute lung injury.

BACKGROUND: A clinically relevant increase of PaO subset2 or decrease of pulmonary vascular resistance (PVR) upon inhalation of NO (iNO) does occur in only 60 to 80% of patients with acute lung injury. The mechanisms for divergent responses of different patients have not yet been fully elucidated. Since NO mediates its pulmonary effects by stimulating soluble guanylate cyclase, thereby increasing levels of cyclic guanosinemonophosphate (cGMP), we hypothesized that pulmonary cGMP production upon iNO might be suppressed in patients not responding to iNO treatment. METHODS: After approval by the local ethical committee and after informed consent had been obtained, both arterial and mixed-venous cGMP levels were analyzed in 13 patients in whom iNO was administered to treat pulmonary hypertension and/or hypoxemia due to acute respiratory distress syndrome (n = 11) or reperfusion injury following lung transplantation (n = 2). Both cardiorespiratory variables and cGMP concentrations were documented simultaneously at baseline, 15 min after inhalation of 8 ppm of NO, and 15 min after withdrawal of NO, respectively. RESULTS: Inhaled NO resulted in a significant increase in PaO(2)/FiO(2) and a decrease in PVR. Arterial and mixed venous concentration of cGMP (median) also increased significantly upon iNO from 2.5 to 6.5 nM (p <0.05) and from 3.0 to 5.7 nM (p <0.05), respectively. Theses effects were fully reversible after withdrawal of iNO. No gradients between arterial and mixed venous cGMP concentrations were detected (p = 0.12). Regression analysis showed no relationship between baseline arterial cGMP concentrations and changes of either PaO(2)/FiO(2) (p = 0. 62) or PVR (p = 0.91). Similarly, no relationship was found between the rise of arterial cGMP concentration subsequent to iNO and corresponding changes of PaO(2) (p = 0.40) or PVR (p = 0.74), respectively. CONCLUSION: Inhalation of NO significantly stimulates soluble guanylate cyclase within the lungs in patients with acute lung injury. However, neither baseline cGMP nor its rise during treatment with inhaled NO can predict the clinical efficacy of iNO in humans. Furthermore, the fact that increased cGMP concentrations were detected during administration of iNO in mixed venous blood (i.e. pulmonary inflow) strongly suggest that the pharmacological effects of iNO are not fully selective for the lungs, but may also affect extrapulmonary organs.

Acute Disease↗
PubMed1999

Lung procurement by low-potassium dextran and the effect on preservation injury. Munich Lung Transplant Group.

BACKGROUND: This clinical study was performed to evaluate the effect of low-potassium dextran (LPD) solution on organ function in human lung transplantation. METHODS: A total of 80 patients were included in this study. Donor lungs were flushed with Euro-Collins (EC) solution in 48 cases or LPD (Perfadex) in 32 cases. Subsequently, single- (EC: n = 31; LPD: n = 15) or double-lung transplantations (EC: n = 17; LPD: n = 17) were performed. The evaluation parameters of transplant function were the reperfusion injury score (grade I to V); the alveolar/arterial oxygen ratio; the duration of respirator therapy; and the length of intensive care treatment and survival. RESULTS: Incidence and severity of reperfusion injury score were more severe in the EC group (31 of 48: grade I: n = 13; II: n = 8; III: n = 5; IV: n = 2; V: n = 3; LPD group: 17 of 32 patients; grade I: n = 12; II: n = 1; III: n = 3; IV: n = 0 grade V: n = 0), leading to death in three patients. In the LPD group, despite of the use of cardiopulmonary bypass, alveolar/arterial oxygen ratio values were significantly (P = 0.009) better during the early postoperative phase. Thirty-day mortality was 12% in the EC group and 6% in the LPD group. The one-year survival rate was 79% after the use of LPD (vs. EC: 62%). CONCLUSIONS: Graft preservation using LPD leads to better immediate and intermediate graft function after pulmonary transplantation and also results in better long-term survival.

Adult↗
PubMed1999

Optimization of the immunosuppressive protocol after lung transplantation.

BACKGROUND: The successful use of tacrolimus (Tac)-based immunosuppressive therapy in organ transplantation and our own positive experience in heart transplantation led us to investigate regimens including this agent at our center for lung transplantation. METHODS: From 1991 to 1998, 86 patients underwent lung transplants at our center and 78 of them were included in this analysis. The first 34 patients were treated with cyclosporin (CsA), azathioprine (Aza), and rabbit antilymphocyte globulin; the subsequent 30 patients received Tac with Aza, and the most recent 12 patients Tac with mycophenolate mofetil (MMF). In addition, all patients received prednisone. RESULTS: The number of acute rejection episodes per 100 patient days was 1.5, 0.6, and 0.3 for three treatment groups, respectively. Similarly, the incidence of refractory acute rejection per 100 patient days was lower in both Tac groups (0.20, 0.03, and 0, respectively). Freedom from acute rejection was highest in the Tac-MMF group (P=0.0037 vs. Tac/Aza, P=0.0007 vs. CsA/Aza). Freedom from recurrent acute rejection was significantly higher in both Tac groups (P=0.027 Tac/ Aza vs. CsA/Aza and P=0.025 Tac/MMF vs. CsA/Aza). The incidence of infections per 100 patient days was similar (0.8, 0.5, and 0.8) in all three treatment groups, with a similar distribution of fungal, bacterial, and viral infections. Freedom from infection also showed no difference. The survival rate was significantly higher for the Tac population, with actuarial 1- and 3-year survival rates of 93% and 71%, compared with the CsA group (71% and 51%, respectively, P=0.04). Prevalence of renal dysfunction (creatinine >2.0 mg/ dL) was 18%, 13%, and 0% in the 3 treatment groups, respectively. The development of glucose metabolism disorders was lower in the CsA group than in the Tac-Aza group (15% vs. 27%, P<0.05). CONCLUSIONS: Tac-based immunosuppressive therapy results in a lower rate of acute rejection after pulmonary transplantation, with similar infection rates and a slightly higher incidence of new onset diabetes mellitus compared with CsA-based therapy.

Acute Disease↗
PubMed1999

Comparison of five sedation scoring systems by means of auditory evoked potentials.

OBJECTIVE: To review five sedation scoring systems and to determine their correlation with an objective method for assessing the level of sedation by means of auditory evoked potentials (AEP) in critically ill patients. DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit in a university hospital. PATIENTS: Ninety-five consecutive patients requiring sedation during intensive care therapy. MEASUREMENTS AND RESULTS: Previous studies have shown that auditory evoked potentials, especially latencies of the midlatency component N(b), could serve as an indicator of depth of anaesthesia. In the present study we used this electrophysiological method to evaluate sedation during intensive care therapy. Changes in latency of peak N(b) were compared with various levels of sedation assessed by five established sedation scoring systems. As in anaesthesia, latencies of N(b) increased with increasing depth of sedation. Among the scoring systems, the one developed by Ramsay correlated best with changes in N(b) latency (r2=0.68). The coefficient of determination, r2, of the other scores ranged from 0.56 to 0.61. CONCLUSION: For the assessment of sedation, several scoring systems have been introduced into clinical practice, but the differentiation of deeper sedation levels, especially, remains poor. In this study we compared auditory evoked potentials, as an objective method with which to assess the level of sedation, with five different sedation scoring systems. In comparison with changes in latency of the midlatency component N(b), Ramsay's sedation score showed the closest correlation. Objective electrophysiological monitoring is desirable during long-term sedation.

APACHE↗
PubMed1999

Sensitivity and specificity of a screening test to document traumatic experiences and to diagnose post-traumatic stress disorder in ARDS patients after intensive care treatment.

OBJECTIVE: Many survivors of critical illness and intensive care unit (ICU) treatment have traumatic memories such as nightmares, panic or pain which can be associated with the development of posttraumatic stress disorder (PTSD). In order to simplify the rapid and early detection of PTSD in such patients, we modified an existing questionnaire for diagnosis of PTSD and validated the instrument in a cohort of ARDS patients after long-term ICU therapy. DESIGN: Follow-up cohort study. SETTING: The 20-bed ICU of a university teaching hospital. PATIENTS: A cohort of 52 long-term survivors of the acute respiratory distress syndrome (ARDS). INTERVENTIONS AND MEASUREMENTS: The questionnaire was administered to the study cohort at two time points 2 years apart. At the second evaluation, the patients underwent a structured interview with two trained psychiatrists to diagnose PTSD according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. The reliability and validity of the questionnaire was then estimated and its specificity, sensitivity and optimal decision threshold determined using receiver operating characteristic (ROC) curve analyses. RESULTS: The questionnaire showed a high internal consistency (Crohnbach's alpha = 0.93) and a high test-retest reliability (intraclass correlation coefficient alpha = 0.89). There was evidence of construct validity by a linear relationship between scores and the number of traumatic memories from the ICU the patients described (Spearman's rho = 0.48, p < 0.01). Criterion validity was demonstrated by ROC curve analyses resulting in a sensitivity of 77.0% and a specificity of 97.5% for the diagnosis of PTSD. CONCLUSIONS: The questionnaire was found to be a responsive, valid and reliable instrument to screen survivors of intensive care for PTSD.

APACHE↗
PubMed1999

Effects of noninvasive positive pressure ventilatory support in non-COPD patients with acute respiratory insufficiency after early extubation.

OBJECTIVE: To investigate the effects of noninvasive positive pressure ventilation (NPPV) on pulmonary gas exchange, breathing pattern, intrapulmonary shunt fraction, oxygen consumption, and resting energy expenditure in patients with persistent acute respiratory failure but without chronic obstructive pulmonary disease (COPD) after early extubation. DESIGN: Prospective study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: 15 patients after prolonged mechanical ventilation (> 72 h) with acute respiratory insufficiency after early extubation. INTERVENTIONS: Criteria for early extubation were arterial oxygen tension (PaO2) > or = 40 mm Hg (fractional inspired oxygen 0.21), arterial carbon dioxide tension (PaCO2) < or = 55 mm Hg, pH > 7.32, respiratory rate < or = 40 breaths per min, tidal volume (VT) > or = 3 ml/kg, rapid shallow breathing index < or = 190 and negative inspiratory force > or = 20 cmH2O. After extubation, two modes of NPPV were applied [continuous positive airway pressure (CPAP) of 5 cmH2O and pressure support ventilation (PSV) with 15 cmH2O pressure support]. MEASUREMENTS AND MAIN RESULTS: Oxygenation and ventilatory parameters improved during both modes of NPPV (p < 0.05): increase in PaO2 of 11 mm Hg during CPAP and 21 mm Hg during PSV; decrease in intrapulmonary shunt fraction of 7% during CPAP and 12% during PSV; increase in tidal volume of 1 ml/kg during CPAP and 4 ml/kg during PSV; decrease in respiratory rate 6 breaths/min during CPAP and 9 breaths/min during PSV. Oxygen consumption (15% during CPAP, 22% during PSV) and resting energy expenditure (12% during CPAP, 20% during PSV) were reduced (p < 0.05). PaCO2 decreased, whereas minute ventilation and pH increased during PSV (p < 0.05). The median duration of NPPV was 2 days. Two patients had to be reintubated. CONCLUSIONS: In non-COPD patients with persistent acute respiratory failure after early extubation, NPPV improved pulmonary gas exchange and breathing pattern, decreased intrapulmonary shunt fraction, and reduced the work of breathing.

APACHE↗
PubMed1999

Tacrolimus (FK506) as primary immunosuppressant after lung transplantation.

BACKGROUND: Our positive experience with tacrolimus (FK 506) in heart transplantation has led to our assessing the use of this medication as a primary immunosuppressant in lung transplantation. 62 of our patients after lung transplantation were included in this study. The first 34 patients were treated with cyclosporine A (CyA), the remaining 28 with tacrolimus. No meaningful differences were found in baseline characteristics. The actuarial one-year survival rate was 70.6% for the CyA group and 92.3% for the tacrolimus group. The number of acute rejection episodes per patient was 1.50 for the CyA group versus 1.18 for the tacrolimus group (p < 0.05). The incidence of infection and their spectrum were comparable in both groups. The most frequently reported adverse events were diabetes mellitus 57% (tacrolimus) vs 23% (CyA), and renal insufficiency (27% vs 15%). Tacrolimus seems to be a more potent immunosuppressant after lung transplantation than CyA; on the other hand, diabetes and nephrotoxicity were diagnosed more frequently using tacrolimus. Although our results are very promising, further follow-up on the incidence of obliterative bronchiolitis is warranted.

Actuarial Analysis↗
PubMed1999

Evaluation of a new continuous thermodilution cardiac output monitor in cardiac surgical patients: a prospective criterion standard study.

OBJECTIVE: To evaluate the accuracy of a new continuous cardiac output monitor in critically ill patients. DESIGN: Criterion standard study. SETTING: Cardiac surgery intensive care unit in a university hospital. PATIENTS: Twenty cardiac surgical patients requiring intensive care treatment with pulmonary artery catheters after surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cardiac output was monitored continuously with a modified pulmonary artery catheter that has a heating filament on the outside of the catheter. Four modes of data processing with different response times ("Normal," "Fast," "FastFilter," and "Urgent" modes) used by the monitoring system. A total of 240 determinations of cardiac output were performed using conventional bolus thermodilution technique; these results were compared with those obtained using three of the four continuous measuring modes available ("Normal," "FastFilter," and "Urgent"). Cardiac output ranged from 3.47 to 15.77 L/min (bolus thermodilution). The mean (bias) +/- SD of differences (precision) for all measurements was 0.40+/-1.26 L/min in the Normal mode (cardiac output <10 L/min: 0.34+/-0.66 L/min), 0.53+/-1.27 L/min in the FastFilter-mode (cardiac output <10 L/min: 0.60+/-0.75 L/min), and 0.63+/-1.34 L/min in the Urgent mode (cardiac output <10 L/min: 0.57+/-0.82 L/min). CONCLUSIONS: Continuous cardiac output measurement using the thermodilution technique is reasonably accurate, reliable, and applicable in routine clinical practice. The values obtained using the Normal mode of the monitor agreed significantly better with the conventional thermodilution method than the results of the two other modes studied (FastFilter and Urgent). In addition, measurements in two patients with cardiac output values of >10 L/min did not agree with the results of the bolus thermodilution method.

Adult↗
PubMed1999

Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.

OBJECTIVE: To investigate the effects of stress doses of hydrocortisone on the duration of vasopressor therapy in human septic shock. DESIGN: Prospective, randomized, double-blind, single-center study. SETTING: Twenty-bed multidisciplinary intensive care unit in a 1400-bed university hospital. PATIENTS: Forty consecutive patients who met the ACCP/SCCM criteria for septic shock. An additional criterion for inclusion in the study was vasopressor support and high-output circulatory failure with a cardiac index of >4 L/min/m2 after fluid resuscitation (pulmonary capillary wedge pressure: 12-15 mm Hg) and without the use of positive inotropes such as dobutamine or dopexamine. The primary study end point was the time to cessation of vasopressor support (norepinephrine or epinephrine in any dose, dopamine > or = 6 microg/kg/min). Secondary study end points were the evolution of hemodynamics and the multiple organ dysfunction syndrome (MODS). The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. MODS was described by the Sepsis-related Organ Failure Assessment score. INTERVENTIONS: All eligible patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started with a loading dose of 100 mg given within 30 mins and followed by a continuous infusion of 0.18 mg/ kg/hr. When septic shock had been reversed, the dose of hydrocortisone was reduced to 0.08 mg/kg/hr. This dose was kept constant for 6 days. As soon as the underlying infection had been treated successfully or sodium serum concentrations had increased to >155 mmol/L, the hydrocortisone infusion was tapered in steps of 24 mg/day. Physiologic saline solution was the placebo. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen-derived variables were measured at previously defined time points over a study period of 5 days. Relevant clinical and laboratory measurements were registered for a study period of 14 days to assess the evolution of organ dysfunction. Baseline data at recruitment did not differ between the two groups. Shock reversal was achieved in 18 of the 20 patients treated with hydrocortisone vs. 16 of the 20 patients treated with placebo. Hydrocortisone significantly reduced the time to cessation of vasopressor support. The median time of vasopressor support was 2 days (1st and 3rd Quartiles, 1 and 6 days) in the hydrocortisone-treated group and 7 days (1st and 3rd Quartiles, 3 and 19 days) in the placebo group (p = .005 Breslow test). There was a trend to earlier resolution of the organ dysfunction syndrome in the hydrocortisone group. CONCLUSIONS: Infusion of stress doses of hydrocortisone reduced the time to cessation of vasopressor therapy in human septic shock. This was associated with a trend to earlier resolution of sepsis-induced organ dysfunctions. Overall shock reversal and mortality were not significantly different between the groups in this low-sized single-center study.

Adult↗
PubMed1999

Recombinant human growth hormone for reconditioning of respiratory muscle after lung volume reduction surgery.

OBJECTIVE: To investigate the effects of recombinant human growth hormone (rHGH) as a "rescue treatment" in an end-stage chronic obstructive pulmonary disease patient after prolonged weaning failure. DESIGN: Descriptive case report. SETTING: Fifteen-bed intensive care unit in a university hospital. PATIENT: A 62-year-old man with end-stage chronic obstructive pulmonary disease and pulmonary emphysema after lung reduction surgery and prolonged weaning failure after long-term mechanical ventilation. INTERVENTIONS: After 42 days of unsuccessful weaning from the respirator, rHGH (27 IU/day, 0.3 IU/kg body weight/day) was administered for 20 days through a subcutaneous injection in addition to standard intensive care. MEASUREMENTS AND MAIN RESULTS: In addition to daily routine laboratory studies, the visceral proteins prealbumin, retinol-binding protein, and transferrin, and nitrogen balance were measured twice a week, as were the thyroid hormones triiodothyronine, thyroxine, and thyroid-stimulating hormone, plasma insulin levels, and the insulin-like growth factor (IGF)-1 binding proteins IGF-BP1 and IGF-BP3. IGF-1 was measured from day 1 to day 4 of rHGH administration. Nutritional support was guided by indirect calorimetry. Additionally, weaning variables such as peak expiratory flow rate and expiratory tidal volume were measured noninvasively. T-piece weaning trials were carried out daily until respiratory muscle fatigue occurred. IGF-1 increased in response to rHGH stimulation, from 103 to 230 microg/mL, within 4 days. The carrier protein IGF-BP3 increased from 126 to 283 mg/L at the end of the study period, and the inhibiting IGF-BP1 decreased initially from 19 to 14 mg/L and then increased until the end of the study to 31 mg/L. Nitrogen balance increased initially from 4.6 to 13.6 g/24 hrs and thereafter decreased until the end of rHGH treatment to 8.3 g/24 hrs. Resting energy expenditure increased from 1800 to 2300 kcal/24 hrs. Peak expiratory flow rate increased from 0.69 to 0.88 L/sec. The expiratory tidal volume showed a slight increase during the study period during the daily decrease of pressure support on the ventilator setting. Respiratory muscular strength increased beginning 10 days after rHGH therapy was started. From this point, T-piece weaning trials could be prolonged almost daily. The patient was extubated successfully on postoperative day 75. CONCLUSIONS: This case report shows that after a prolonged catabolic state and long-term mechanical ventilation, administration of rHGH not only enhances the response of protein metabolism but improves respiratory muscular strength. Therefore, it may reduce the duration of mechanical ventilation in selected patients.

Energy Metabolism↗
PubMed1999

The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder and health-related quality of life in survivors.

OBJECTIVES: The exposure to intense physical and psychological stress during intensive care can result in posttraumatic stress disorder (PTSD) in survivors. Cortisol is a biological stress mediator that can have a protective effect during severe stress. The administration of stress doses of hydrocortisone during treatment in the intensive care unit could theoretically result in a lower incidence of PTSD. We tested this hypothesis in survivors of septic shock. DESIGN: A retrospective case-controlled analysis. SETTING: A 20-bed multidisciplinary intensive care unit of a tertiary-care university hospital. PATIENTS: We identified 27 patients who received standard therapy for septic shock. These patients served as controls and were compared with an equal number of patients who received hydrocortisone in addition to standard treatment. These patients were selected from our database with regard to age (+/-4 yrs), gender, and cause of septic shock to be as similar as possible with control patients. INTERVENTIONS: Patients from the hydrocortisone group had received stress doses of hydrocortisone (100 mg bolus, followed by 0.18 mg/kg/hr) in addition to standard treatment. Patients from the control group received standard protocol-driven treatment only. PTSD was diagnosed with the Posttraumatic Stress Syndrome-10 inventory, a self-report scale for diagnosis of PTSD. Health-related quality of life was measured using the Medical Outcomes Study Short-Form Survey (Medical Outcomes Trust, Boston, MA), which consists of 36 questions. MEASUREMENTS AND MAIN RESULTS: Patients who received hydrocortisone during septic shock had a significantly lower incidence of PTSD than patients who received standard treatment only (5 of 27 vs. 16 of 27; p = .01) and had significantly higher scores on the mental health index of the Medical Outcomes Study Short-Form health-related quality-of-life questionnaire (68 vs. 44 points; p = .009). CONCLUSIONS: Data from this study support the hypothesis that the administration of stress doses of hydrocortisone in doses equivalent to the maximal endocrine secretion rate during septic shock reduces the incidence of PTSD and improves emotional well-being in survivors. This hypothesis should be tested in a prospective randomized trial.

APACHE↗
PubMed1999

Cardiopulmonary exercise testing before and after lung and heart-lung transplantation.

Heart-lung (HLT) and lung transplantation (LT) have been shown to be effective procedures for patients with end-stage cardiopulmonary disorders. As yet, few data exist on the exercise performance of patients before and after thoracic transplantation except with regard to 6-min walk tests. In this article we report cardiopulmonary exercise test results of lung and heart-lung transplant recipients in comparison with their pretransplant values. We studied 103 consecutive recipients of single-lung (n = 46), bilateral lung (n = 32), and heart-lung (n = 25) transplants. Cardiopulmonary exercise testing with a cycle ergometer was performed before and shortly after surgery. Before transplantation, all patients showed severe exercise intolerance and markedly impaired parameters reflecting cardiopulmonary function (e.g., work capacity: 20 +/- 11% predicted; oxygen uptake: 34 +/- 12% predicted; oxygen pulse: 50 +/- 18% predicted; functional dead space ventilation: 57 +/- 10% of minute ventilation; alveolar-arterial oxygen difference during exercise: 79 +/- 15 mm Hg). At 55 +/- 9 d after transplantation, transplant recipients reached maximum oxygen uptakes in the range of 22 to 71% of predicted values; the peak oxygen uptake was increased after transplantation (13.1 +/- 3.4 ml/min/kg versus 10.4 +/- 3.8 ml/min/kg; p < 0.001). Work capacity, oxygen pulse, tidal volume, and peak minute ventilation did not differ in patients following single- or double-lung tranplantation or HLT. Ventilatory factors did not appear to limit exercise capacity in any group. Despite the persistent limitations in aerobic capacity and work rate seen in many of the recipients, cardiopulmonary performance is reasonably well restored shortly after LT and HLT.

Adult↗
PubMed1999

Bronchiolitis obliterans syndrome after (heart-)lung transplantation. Impaired antiprotease defense and increased oxidant activity.

Increased numbers of neutrophils are a common finding in bronchoalveolar lavage fluid (BALF) samples obtained from patients after (heart-)lung transplantation [(H)LTX]. Since proteases and reactive oxygen species secreted by neutrophils are capable of causing substantial damage to the lung tissue if not counterbalanced by the antiprotease and antioxidant screen, we hypothesized that neutrophil products may play a role in the development of obliterative bronchiolitis (OB). A total of 72 BALF samples obtained from 33 patients after (H)LTX were evaluated. Sixteen of these patients were suffering from bronchiolitis obliterans syndrome (BOS) at the time of bronchoalveolar lavage (BAL). As a control, BALF samples from 17 healthy volunteers were analyzed. Anti-neutrophil elastase (NE) activity was quantified by a titration assay. Concentrations of alpha(1)-protease inhibitor (API), secretory leukocyte protease inhibitor (SLPI), NE-API complex, and myeloperoxidase (MPO) were measured by ELISA. Oxidized methionine [Met(O)] was quantified by high-performance liquid chromatography (HPLC). Epithelial lining fluid (ELF) from patients suffering from BOS showed significantly increased neutrophil counts, significantly elevated concentrations of NE-API complex and Met(O), and a significant decrease in the concentration of SLPI. Furthermore, a trend toward an increased NE activity and MPO concentration was observed. These findings suggest that neutrophils may be involved in the development of BOS.

Bronchiolitis Obliterans↗
PubMed1998

Expression of adhesion molecules on circulating polymorphonuclear leukocytes during orthotopic liver transplantation.

After ischemia-reperfusion, polymorphonuclear leukocytes (PMNLs) become activated by inflammatory mediators, adhere to the vascular endothelium via the interaction of specific adhesion molecules, and cause tissue injury by the release of cytotoxic oxygen radicals and enzymes. Results obtained in animal experiments suggest a key role for PMNLs in ischemia-reperfusion injury of transplanted livers; therefore, we studied the expression of adhesion molecules on circulating PMNLs (beta2-integrins [CD18] and L-selectin [CD62L]) in 20 patients undergoing orthotopic liver transplantation (study group). To determine the effects of surgical trauma to the liver in the absence of ischemia and reperfusion, the expression of PMNL adhesion molecules was measured in 10 patients scheduled for elective partial liver resection without hepatic vascular exclusion (control group). Patients were classified as responders or nonresponders based on changes in the expression of adhesion molecules elicited by reperfusion. In the control group, all patients remained nonresponders, showing that surgical trauma of the liver alone does not cause activation of circulating PMNLs. In contrast, 8 of 20 patients in the study group were classified as responders. In responders, postoperative serum liver enzyme activities were significantly higher than in nonresponders, indicating that activation of PMNL was associated with damage to hepatocellular integrity. Because expression of adhesion molecules was already changed during surgery, monitoring of the expression of beta2-integrins and L-selectin on circulating PMNLs during orthotopic liver transplantation might be useful in prediction of early graft dysfunction.

Adolescent↗